The availability of transgenic and gene targeting methods, and the large number of spontaneous and induced mutant mice with altered neural development, have led to new insights into the genetic pathways involved in patterning events and cell differentiation in the mouse CNS. The same genetic techniques also are being used increasingly to produce mouse models of human degenerative brain diseases. Lacking are effective, non- invasive methods of analyzing the dynamic, 3-D processes involved in mouse neural development and brain diseases. Lacking are effective, non- invasive methods of analyzing the dynamic, 3-D processes involved in mouse neural development and brain disease. Clinical evaluation of human brain development and disease relies heavily on medical imaging technologies, with ultrasound imaging providing the means for detecting developmental defects, and magnetic resonance (MR) imaging techniques being widely used for non-invasive imaging of the anatomical structure and function of the postnatal human brain. We are developing high resolution in vivo ultrasound and MR micro-imaging methods for visualizing the developing mouse brain. The broad goals of this project are to develop a unique combination of ultrasound and MR micro-imaging techniques to analyze neural development and degeneration in the mouse from early embryonic to adult stages. The specific aims are: 1) To develop ultrasound instrumentation to optimize resolution for imaging early stage mouse embryos. 2) To develop robust 3-D ultrasound imaging methods for in utero mouse embryo imaging. 3) To develop optimal rf coils for 7 Tesla MR micro-imaging of mouse brain development. 4) To optimize a set of MR pulse sequences for anatomical and functional imaging of the mouse brain. The combination of recent breakthroughs in mouse genetics together with this high resolution ultrasound and MR micro-imaging technology will provide powerful new tools for studying mouse neural development and mouse models of human neurodegenerative disease, and for exploring in utero cell and gene therapy approaches.